Potential Mechanism of Shikonin in Treatment of Cancer Based on Bioinformatics and in Vitro Experiments
Objective:Shikonin(SHK),a naphthoquinone pigment-type active ingredient of lithospermum root,has anti-tumor ac-tivity.This study aims to identify novel targets of SHK in hepatocellular carcinoma(LIHC),prostate adenocarcinoma(PR AD),and colon adenocarcinoma(COAD)using bioinformatics methods and in vitro experiments.Methods:Intersection genes of SHK and three kinds of cancer were screened from GeneCard and TCGA databases.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses and protein-protein interaction(PPT)network construction were performed.The study detected the inhibitory effect of SHK on HepG2,LNCaP C4-2,and HT-29 cells through in vitro experiments and analyzed the effect of SHK on cell apoptosis and expression of predicted target genes.Results:SHK significantly inhibited the proliferation of three kinds of cancer cells and achieved the anti-tumor effect by regulating the expression of CDKN1A and other genes,which was consistent with the prediction of bioinformatics.In addition,the Kaplan-Meier survival curve further showed that CDKN1A and other genes were important targets of SHK affecting the survival of patients with cancer.CDKN1A and BCL-2 were the core targets of SHK in inhibiting the proliferation and invasion of cancer cells.Conclusion:SHK may induce cancer cell apoptosis through the P53/CDKN1A and BCL-2/BAX signaling pathways.The study reports the anti-tumor targets and underlying mechanisms of SHK,which provides preliminary evidence for the application of SHK-containing Chinese herbal medicine as a potential anti-tumor drug.
万方数据
维普
